Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer

Abstract

Recently, gene fusions between the androgen responsive gene TMPRSS2 and members of the ETS-family of DNA-binding transcription factor genes were found in prostate cancer. Recurrent fusions were identified between the 5'-noncoding region of TMPRSS2 and ERG, or less frequently ETV1 or ETV4, resulting in overexpression of normal or truncated ETS-proteins. Herein, we have analyzed a series of 50 prostate cancer samples for expression of TPRSS2-ERG and TMPRSS2-ETV1 fusion transcripts. RT-PCR analysis revealed TMPRSS2-ERG fusion transcripts in 18 of the 50 tumors (36%). None of the tumors expressed a TMPRSS2-ETV1 fusion. Our findings show that the TMPRSS2-ERG fusion is common in prostate cancer and that the related TMPRSS2-ETV1 fusion is very rare. However, the frequency of ERG-fusions in the present study is somewhat lower than previously observed, indicating heterogeneity with regard to expression of ETS-gene fusions in subsets of prostate cancers. Moreover, clinical follow-up studies showed a clear tendency that fusion-positive tumors were associated with lower Gleason grade and better survival than fusion-negative tumors. Our findings suggest that ERG gene fusions might be of prognostic significance in prostate cancer.